Figure 1. Novel MELK inhibitors.

(A) A quinoline derivative, diethyl 4-(4-acetamidophenylamino) quinoline-3,6-dicarboxylate (compound 1; a commercially available compound), was found to have a moderate inhibitory activity against MELK (IC₅₀ = 4.8 μM) through the high-throughput screening. The subsequent structure-activity relationship study led to the synthesis of a highly potent MELK inhibitor with a novel structure: (B) compound OTSSP167, 1-(6-(3,5-dichloro-4-hydroxyphenyl)-4-((trans-4-((dimethylamino)methyl)cyclohexyl)amino)-1,5-naphthyridin-3-yl)ethanone. The dihydrochloride salt form was used in experiments for OTSSP167.